DESCRIPTION (provided by investigator): Chlamydia trachomatis genital tract infections remain a significant national and global health problem that is especially important in women's reproductive health. Recognition of the role C. trachomatis plays in the development of severe upper genital tract disease coupled with recent observations demonstrating an increase in the incidence of chlamydial genital tract infections associated with the most effective screen and treatment programs highlight the need to learn more about the epidemiology and pathogenesis of chlamydial genital tract disease to ensure the most effective control measures are developed and implemented. We propose to study a murine model of chlamydial genital tract infection to determine if arrested immunity helps explain the increased incidence of chlamydial genital tract infections. In our first aim we will evaluate if early antibiotic intervention impacts development of an immune response to primary infection, susceptibility to reinfection and most importantly development of upper genital tract sequelae and its severity. This aim will be complemented by a second aim, which will examine host genetics in the development of upper genital tract disease. Preliminary data are presented to validate the use of recombinant inbred (BXD) mice as a powerful method to study host factors and disease severity. We have established intervals on mouse chromosomes 3 and 19 that correlate with oviduct and uterine involvement and disease severity. Interestingly, these loci have syntenous intervals on human chromosomes 1 and 11, making it highly likely that the approaches we have chosen to study in mice will have translational relevance to human disease. Results of this study will be important in improving our understanding of arrested immunity and chlamydial genital tract disease, the impact of arrested immunity on upper tract disease severity and the role of host genetic factors in the development of chlamydial upper genital tract disease. PUBLIC HEALTH RELEVANCE: Chlamydia trachomatis is the most frequently reported sexually transmitted infection in the United States and an important public health problem because it causes upper genital tract complications in women. The incidence of chlamydial genital tract infections is increasing in the United Sates at an alarming rate despite implementation of excellent screening and treatment programs during the past 15 years, making it imperative to learn more about why this important human pathogen is so difficult to control. Work proposed in this application is designed to provide new information on why chlamydial genital tract infections are on the rise, why some individuals are more likely to have severe complications of infections than others, and how we can best protect ourselves from this disease by understanding the genetic basis of serious chlamydial disease development and how it may be prevented.